TY - JOUR
T1 - Anti-IFN-α/-ω neutralizing antibodies from COVID-19 patients correlate with downregulation of IFN response and laboratory biomarkers of disease severity
AU - Frasca, Federica
AU - Scordio, Mirko
AU - Santinelli, Letizia
AU - Gabriele, Lucia
AU - Gandini, Orietta
AU - Criniti, Anna
AU - Pierangeli, Alessandra
AU - Angeloni, Antonio
AU - Mastroianni, Claudio M.
AU - d'Ettorre, Gabriella
AU - Viscidi, Raphael P.
AU - Antonelli, Guido
AU - Scagnolari, Carolina
N1 - Funding Information:
We thank all the clinicians who helped to enroll COVID-19 patients and collected clinical data. We are grateful to the staff of the virology laboratories for their collaboration. This work was supported by a grant from the Italian Ministry of Health (COVID-2020-12371817) and from Sapienza University of Rome (ATENEO_RICERCA_2020_CL_HORIZON) to A.G. (Antonelli Guido); by a grant from Sapienza University of Rome (Progetti di ricerca [2019 and 2020]) to S.C. (Scagnolari Carolina); by a grant (Project B/2020/0128 “Molecular and cellular characterization of immune profiles in COVID-19 patients as predictive markers of disease outcome,” Fondo di Beneficenza di Intesa Sanpaolo) to G.L. (Gabriele Lucia). Funding sources were not involved in study design; in the collection, analysis, and interpretation of data; in the writing of this manuscript and in the decision to submit the article for publication. Open Access Funding provided by Universita degli Studi di Roma La Sapienza within the CRUI-CARE Agreement. [Correction added on 10 May 2022, after first online publication: CRUI-CARE funding statement has been added.]
Funding Information:
We thank all the clinicians who helped to enroll COVID‐19 patients and collected clinical data. We are grateful to the staff of the virology laboratories for their collaboration. This work was supported by a grant from the Italian Ministry of Health (COVID‐2020‐12371817) and from Sapienza University of Rome (ATENEO_RICERCA_2020_CL_HORIZON) to A.G. (Antonelli Guido); by a grant from Sapienza University of Rome (Progetti di ricerca [2019 and 2020]) to S.C. (Scagnolari Carolina); by a grant (Project B/2020/0128 “Molecular and cellular characterization of immune profiles in COVID‐19 patients as predictive markers of disease outcome,” Fondo di Beneficenza di Intesa Sanpaolo) to G.L. (Gabriele Lucia). Funding sources were not involved in study design; in the collection, analysis, and interpretation of data; in the writing of this manuscript and in the decision to submit the article for publication.
Publisher Copyright:
© 2022 The Authors. European Journal of Immunology published by Wiley-VCH GmbH.
PY - 2022/7
Y1 - 2022/7
N2 - A significant number of COVID-19 patients were shown to have neutralizing antibodies (NAB) against IFN; however, NAB specificity, fluctuation over time, associations with biochemical and hematological parameters, and IFN gene expression are not well characterized. Binding antibodies (BAB) to IFN-α/-β were screened in COVID-19 patients’ serum. All BAB positive sera, and a subset of respiratory samples, were tested for NAB against IFN-α/-β/-ω, using an antiviral bioassay. Transcript levels of IFN-α/-β/-ω and IFN-stimulated genes (ISGs) were quantified. Anti-IFN-I BAB were found in 61 out of 360 (17%) of patients. Among BAB positive sera, 21.3% had a high NAB titer against IFN-α. A total of 69.2% of anti-IFN-α NAB sera displayed cross-reactivity to IFN-ω. Anti-IFN-I NAB persisted in all patients. NAB to IFN-α were also detected in 3 out of 17 (17.6%) of respiratory samples. Anti-IFN-I NAB were higher in males (p = 0.0017), patients admitted to the ICU (p < 0.0001), and patients with a fatal outcome (p < 0.0001). NAB were associated with higher levels of CRP, LDH, d-Dimer, and higher counts of hematological parameters. ISG-mRNAs were reduced in patients with persistently NAB titer. NAB are detected in a significant proportion of severe COVID-19. NAB positive patients presented a defective IFN response and increased levels of laboratory biomarkers of disease severity.
AB - A significant number of COVID-19 patients were shown to have neutralizing antibodies (NAB) against IFN; however, NAB specificity, fluctuation over time, associations with biochemical and hematological parameters, and IFN gene expression are not well characterized. Binding antibodies (BAB) to IFN-α/-β were screened in COVID-19 patients’ serum. All BAB positive sera, and a subset of respiratory samples, were tested for NAB against IFN-α/-β/-ω, using an antiviral bioassay. Transcript levels of IFN-α/-β/-ω and IFN-stimulated genes (ISGs) were quantified. Anti-IFN-I BAB were found in 61 out of 360 (17%) of patients. Among BAB positive sera, 21.3% had a high NAB titer against IFN-α. A total of 69.2% of anti-IFN-α NAB sera displayed cross-reactivity to IFN-ω. Anti-IFN-I NAB persisted in all patients. NAB to IFN-α were also detected in 3 out of 17 (17.6%) of respiratory samples. Anti-IFN-I NAB were higher in males (p = 0.0017), patients admitted to the ICU (p < 0.0001), and patients with a fatal outcome (p < 0.0001). NAB were associated with higher levels of CRP, LDH, d-Dimer, and higher counts of hematological parameters. ISG-mRNAs were reduced in patients with persistently NAB titer. NAB are detected in a significant proportion of severe COVID-19. NAB positive patients presented a defective IFN response and increased levels of laboratory biomarkers of disease severity.
KW - COVID-19
KW - ISG
KW - Interferon
KW - autoantibodies, SARS-CoV-2
KW - binding antibodies
KW - neutralizing antibodies
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U2 - 10.1002/eji.202249824
DO - 10.1002/eji.202249824
M3 - Article
C2 - 35419822
AN - SCOPUS:85128826578
SN - 0014-2980
VL - 52
SP - 1120
EP - 1128
JO - European Journal of Immunology
JF - European Journal of Immunology
IS - 7
ER -